The immunodeficiency of aging and Alzheimer's Disease (AD) are due to developing defects in lymphoid cells which present their proliferative responses to an immunogen. Since most immunologic investigations have been limited to stimulus-response experiments, the objective of this study is to investigate into basic biochemical and nutritional factors priming the immunodeficiency of AD and aging. The response of lymphocytes to immunogen may be measured as incorporation of (3H)-thymidine (TdR) into replicating DNA while the stimulated cell undergoes blastogenesis. A large number of biochemical events must supervene between the initial stimulus and the final responses. This study proposes: Hypothesis I. AD Lymphocytes show a decreased response to PHA because they are defective in mitochondrial production of ATP; Hypothesis II. Mitochondria isolated from AD lymphocytes are defective in respiratory rate; Hypothesis III. Mitochondria isolated from AD lymphocytes are defective in trace element contents and size; Hypothesis IV. Kinetic experiments using pharmacological agents to test whether cAMP level changes would bring about a better immune response in AD lymphocytes; Four known risk factors of AD are old age, Down's Syndrome (DS), family with history of DS and Alzheimer's Disease. Unlike cancer and heart disease that many countries already have effective public health campaigns for reducing and modifying risk factors, the aforementioned risk factors for AD are unfortunately not modifiable. We attempt to discover additional risk factors which could be modifiable by better life style and nutrition thereby improving immunity so that prevention of AD may seem a rather attainable goal. Therefore we propose Hypothesis V. A longitudinal 4 year, follow-up nutritional assessments and interventions of AD patients. Students under this MBRS subproject will be motivated to pursue their careers in geriatric medicine, health care and research. They will receive training in laboratory skills of biochemistry, nutrition and immunology and also obtain clinical, social and practical nutritional counseling experiences as they conduct their studies. Their findings will help to prevent or to meliorate immunodeficiency of AD patients and aged humans.